This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose to investigate the organization and function of proteins and protein complexes within cells in order to elucidate how atomic-scale dynamics drives large-scale cellular processes. For our studies, we employ the highly efficient molecular dynamics (MD) program NAMD, developed in our lab, to carry out large-size and long-time simulations of seven key processes taking place in nearly all cellular organisms. MD affords a simultaneous resolution in both time and space for the study of these processes unattainable by experimental techniques. With our recently developed MD Flexible Fitting method, we join MD and experiment, taking atomic-resolution, but unphysiological, crystal structures and fit them to lower resolution, but physiologically relevant, electron-microscopy data, yielding structures representing functional macro-molecular systems. Actually, all of our projects involve close collaboration with experimentalists. We propose to study (i) how proteins fold from an unfolded starting sequence, (ii) how proteins are synthesized by the ribosome and (iii) how nascent proteins are exported into cellular membranes or excreted. On a larger scale, we seek to study how cells shape their internal membranes, by proteins called (iv) BAR domains or by (v) integral membrane proteins. Lastly, we investigate key components of transcription in cells, (vi) helicases, that unwind double stranded DNA, and (vii) nuclear pore proteins that control export and import between a cells cytoplasm and nucleoplasm.